PITX2 p.Phe99fs
c.296_297del · VCV3344394
Likely pathogenic
No assertion criteria
Classification
Likely pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
PITX2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 3 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 1.6, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- PITX2
- Protein
- p.Phe99fs
- Coding
- c.296_297del
- MANE Select
- NM_000325
- Type
- Deletion
- Location
- chr4:110621278 (GRCh38)
- Gene constraint
- LOEUF 0.41 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.59 · 3 PDB
- Residue 99
- a DNA-binding region; the 'disordered' region; an α-helix
Disease context
PITX2-related disorder
Similar variants
- PITX2 p.Phe99Ser Likely pathogenic ★ same residue
- PITX2 p.Thr110fs Likely pathogenic ★ same condition
- PITX2 p.Asp29fs Uncertain significance same condition
- PITX2 p.Arg122His Pathogenic ★★ same condition
- PITX2 c.*454C>T Benign ★★ same condition
- PITX2 p.Ser206= Benign/Likely benign ★★ same condition
- PITX2 p.Arg144Leu Likely pathogenic ★ same condition
- PITX2 p.Gln103Arg Likely pathogenic ★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pitx2-p-phe99fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown